Peripheral blood leukocytes (PBL) from adult asymptomatic, HIV-infected patients (HIV+) exhibit a complex pattern of T helper cell (Th) dysregulation that:a) involves a sequential loss of function to recall antigens, then to HLA alloantigens, and finally to mitogens; b) is predictive for progression toward AIDS; and c) has also been verified in pediatric AIDS development (although progression in children appears to be more rapid). The earliest Th defect in the HIV + is associated with a CD8+ T cell that down-regulates self-restricted Th function, and produces a soluble factor that also down-regulates the same Th function. Studies of antigen-presenting cell (APC) function were performed in HIV+ and AIDS patients. No APC defect was detected in HIV+, but 2/3 of AIDS patients exhibited one of two different types of APC defects. A sensitive HIV-specific Th assay has been developed that can detect exposure to HIV up to 14 months before anti-HIV antibody is detected. This assay has been used to detect exposure to HIV in high-risk seronegative individuals and to monitor T cell immunity in uninfected volunteers immunized with an AIDS trial vaccine. Strong Th immunity was detected in the vaccinees immunized with a recombinant gp160 subunit vaccine.